Quantitative Assessment of Liver Function after Ischemia-Reperfusion Injury and Partial Hepatectomy in Rats

Abstract

Liver function after hepatic ischemia-reperfusion (I/R) injury and partial liver resection (PHx) is influenced by the extent of PHx, hepatocellular damage, and liver regeneration. This study investigates the effect of minor PHx with increasing degrees of I/R-induced damage on postoperative liver function parameters and compares the indocyanine green (ICG) clearance test with (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) for quantitative measurement of hepatic function in a standardized rat model. Rats were subjected to 70% partial liver I/R combined with resection of the nonischemic lobes. Various degrees of hepatic damage were induced by 0, 15, 30, 45, and 60 min ischemia. Prothrombin time and bilirubin were used as indirect parameters of liver function. (99m)Tc-mebrofenin HBS and ICG clearance were used as dynamic quantitative liver function tests. After 24 h reperfusion hepatocellular damage increased with prolonged ischemia times. Hepatocellular damage and liver regeneration were closely interrelated. Moderate I/R-induced damage enhanced regeneration, while extensive damage debilitates the regenerative capacity. PHx alone resulted in no significant decrease in liver uptake function measured by HBS or ICG. Increasing severity of hepatic I/R injury had a differential effect on ICG clearance and (99m)Tc-mebrofenin uptake and excretion. The specific impact of 30% PHx combined with progressive ischemia times is different for each liver function test. Albeit (99m)Tc-mebrofenin HBS and the ICG clearance test provide complementary quantitative information to biochemical parameters, they only quantify one or two components of liver function. ICG and (99m)Tc-mebrofenin uptake profiles differed significantly, suggesting that the specific hepatic transporters may be distinct.